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TLR3 Gene

protein-coding   GIFtS: 72
GCID: GC04P186990

Toll-Like Receptor 3
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Aliases
for TLR3 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Toll-Like Receptor 31 2
IIAE22 5
CD2832
CD283 Antigen3

External Ids:    HGNC: 118491   Entrez Gene: 70982   Ensembl: ENSG000001643427   OMIM: 6030295   UniProtKB: O154553   

Export aliases for TLR3 gene to outside databases

Previous GC identifers: GC04P188024 GC04P187670 GC04P187574 GC04P187686 GC04P187365 GC04P187227 GC04P182742


Summaries
for TLR3 gene

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TLR3 Gene:
The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role
in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans
and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs)
that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of
effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly
expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It
recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of
type I interferons. It may thus play a role in host defense against viruses. Use of alternative polyadenylation
sites to generate different length transcripts has been noted for this gene. (provided by RefSeq, Jul 2008)

GeneCards Summary for TLR3 Gene:
TLR3 (toll-like receptor 3) is a protein-coding gene. Diseases associated with TLR3 include hiv1 infection, and herpes simplex encephalitis 2. GO annotations related to this gene include double-stranded RNA binding and receptor activity. An important paralog of this gene is ENSG00000173366.

UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455
Function: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response
against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a
nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter
TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the
inflammatory response

summary for TLR3 Gene:
Toll-like receptors (TLRs) are single transmembrane cell-surface receptors, which have a key role in the
innate immune system. TLRs generally exist as homodimers (although TLR2-TLR6 heterodimers have been
reported) and are found on immune cells such as macrophages, B lymphocytes and mast cells. Toll-like
receptors are activated by molecules associated with biological threat and are highly specific towards
evolutionary conserved entities on microbes, such as bacterial cell-surface lipopolysaccharides, flagella
and unmethylated CpG islands. It has been suggested that some toll-like receptors may have endogenous
ligands, such as Hsp60 and fibrinogen, and this has promoted speculation that endogenous toll-like receptor
activators may have a pathological role in autoimmune disease. Activation of toll-like receptors initiates
downstream signaling cascades, initially via the adapter molecules MyD88, Trap, Trif and Tram, which
converge on the PI 3-K and NF-kappaB pathways and regulate intracellular kinases and gene expression. This
can stimulate an inflammatory and/or antigen-specific immune response. The signaling cascade coupled to
toll-like receptor activation is very similar to that of interleukin-1 receptor (IL-1R) activation.

Gene Wiki entry for TLR3 (TLR 3) Gene


Genomic Views
for TLR3 gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000004.12  NT_016354.20  NC_018915.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the TLR3 gene promoter:
         AP-1   ATF-2   NF-AT   NF-AT2   POU2F1   POU2F1a   NF-AT3   STAT3   c-Jun   NF-AT1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: TLR3 promoter sequence
   Search Chromatin IP Primers for TLR3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TLR3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 4q35   Ensembl cytogenetic band:  4q35.1   HGNC cytogenetic band: 4q35

TLR3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TLR3 gene location

GeneLoc information about chromosome 4         GeneLoc Exon Structure

GeneLoc location for GC04P186990:  view genomic region     (about GC identifiers)

Start:
 186,990,306 bp from pter      End:
 187,009,223 bp from pter
Size:
 18,918 bases      Orientation:
 plus strand

Proteins
for TLR3 gene

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455 (See protein sequence)
Recommended Name: Toll-like receptor 3 precursor  
Size: 904 amino acids; 103829 Da
Subunit: Monomer and homodimer; dimerization is triggered by ligand-binding, the signaling unit is composed of one
ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the
ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the
interaction is required for transport from the ER to the endosomes. Interacts with TICAM1 (via the TIR domain);
mediates TLR3 signaling. Interacts with SRC; upon binding of double-stranded RNA
4 PDB 3D structures from and Proteopedia for TLR3:
1ZIW (3D)        2A0Z (3D)        3ULU (3D)        3ULV (3D)    
Secondary accessions: B2RAI7 E6Y0F0 E6Y0F1 Q4VAL2 Q504W0

Explore the universe of human proteins at neXtProt for TLR3: NX_O15455

Explore proteomics data for TLR3 at MOPED

Post-translational modifications: 

  • Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding1
  • TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between
    amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes1
  • Glycosylation2 at Asn52, Asn57, Asn70, Asn124, Asn196, Asn247, Asn252, Asn265, Asn275, Asn291,
                                 Asn398, Asn413, Asn507, Asn636, Asn662
  • Modification sites at PhosphoSitePlus

    • See TLR3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_003256.1  
    ENSEMBL proteins: 
     ENSP00000296795   ENSP00000423386   ENSP00000423684  
    Reactome Protein details: O15455

    TLR3 Human Recombinant Protein Products:

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    R&D Systems Recombinant & Natural Proteins for TLR3
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for TLR3
    OriGene Custom MassSpec
    OriGene Custom Protein Services for TLR3
    GenScript Custom Purified and Recombinant Proteins Services for TLR3
    Novus Biologicals TLR3 Proteins
    Novus Biologicals TLR3 Lysate
    Sino Biological Recombinant Protein for TLR3
    Sino Biological Cell Lysate for TLR3
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for TLR3

    TLR3 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of TLR3
    R&D Systems Antibodies for TLR3
    Cell Signaling Technology (CST) Antibodies for TLR3 
    OriGene Antibodies for TLR3
    OriGene Custom Antibody Services for TLR3
    Novus Biologicals TLR3 Antibodies
    Abcam antibodies for TLR3
    Cloud-Clone Corp. Antibodies for TLR3
    ThermoFisher Antibody for TLR3
    LSBio Antibodies in human, mouse, rat for TLR3

    TLR3 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for TLR3
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for TLR3
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for TLR3
    Cloud-Clone Corp. CLIAs for TLR3

    Domains /
    Families
    for TLR3 gene

    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    TryGeneCards Plus    		 HGNC Gene Families:
    CD: CD molecules

    IUPHAR Guide to PHARMACOLOGY protein family classification: TLR3
    Toll-like receptor family

    Selected InterPro protein domains (see all 6):
     IPR000483 Cys-rich_flank_reg_C
     IPR000372 LRR-contain_N
     IPR001611 Leu-rich_rpt
     IPR000157 TIR_dom
     IPR027173 TLR3

    Graphical View of Domain Structure for InterPro Entry O15455

    ProtoNet protein and cluster: O15455

    4 Blocks protein domains:
    IPB000157 TIR domain
    IPB000372 Cysteine-rich flanking region
    IPB000483 Cysteine-rich flanking region
    IPB001611 Leucine-rich repeat signature


    UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455
    Domain: ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18
    Similarity: Belongs to the Toll-like receptor family
    Similarity: Contains 22 LRR (leucine-rich) repeats
    Similarity: Contains 1 LRRCT domain
    Similarity: Contains 1 LRRNT domain
    Similarity: Contains 1 TIR domain


    TLR3 for domains           About GeneDecksing


    Function
    for TLR3 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
    About This Section

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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TLR3_HUMAN, O15455
    Function: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response
    against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a
    nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter
    TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the
    inflammatory response

         Genatlas biochemistry entry for TLR3:
    Drosophila transmembrane receptor Toll homolog 3,with the major transcripts,predominantly expressed in placenta
    and pancreas,involved in immune defense

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003725double-stranded RNA binding NAS12054664
    GO:0004872receptor activity TAS10426995
    GO:0004888transmembrane signaling receptor activity NAS12054664
    GO:0005515protein binding IPI16858407
         
    TLR3 for ontologies           About GeneDecksing


    Phenotypes:
         12 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Tlr3):
     behavior/neurological  cardiovascular system  endocrine/exocrine gland  hematopoietic system  homeostasis/metabolism 
     immune system  mortality/aging  muscle  nervous system  reproductive system 
     respiratory system  tumorigenesis 

    TLR3 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for TLR3: Tlr3tm1Flv Tlr3tm1Ttg

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TLR3
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for TLR3

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TLR3
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TLR3

    miRNA
    Products:            		miRTarBase miRNAs that target TLR3:
    hsa-mir-124-3p (MIRT022528)

    Block miRNA regulation of human, mouse, rat TLR3 using miScript Target Protectors
    Search for qRT-PCR Assays for microRNAs that regulate TLR3
    SwitchGear 3'UTR luciferase reporter plasmid: TLR3 3' UTR sequence
    Inhib. RNA
    Products:            		OriGene RNAi products in human, mouse, rat for TLR3
    Predesigned siRNA for gene silencing in human, mouse, rat TLR3

    Gene Editing
    Products:    		DNA2.0 Custom Protein Engineering Service for TLR3

    Clone
    Products:             		 OriGene clones in human, mouse for TLR3 (see all 6)
    OriGene ORF clones in mouse, rat for TLR3
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: TLR3 (NM_003265)
    Sino Biological Human cDNA Clone for TLR3
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TLR3
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TLR3

    Cell Line
    Products:             		GenScript Custom overexpressing Cell Line Services for TLR3
    Browse ESI BIO Cell Lines and PureStem Progenitors for TLR3 
    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TLR3


    Localization
    for TLR3 gene

    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
    About This Section

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    Subcellular locations from UniProtKB/Swiss-Prot
    TLR3_HUMAN, O15455: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    endosome5
    golgi apparatus4
    lysosome4
    plasma membrane4
    vacuole4
    nucleus3
    extracellular2
    peroxisome2
    cytosol1
    mitochondrion1

    Gene Ontology (GO): Selected cellular component terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0005622intracellular ----
    GO:0005737cytoplasm IDA19740627
    GO:0005765lysosomal membrane IDA17897319
    GO:0005789endoplasmic reticulum membrane TAS--

    TLR3 for ontologies           About GeneDecksing


    Pathways & Interactions
    for TLR3 gene

    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TLR3 About   (see all 19)  
    See pathways by source

    SuperPathContained pathways About
    1Toll-like receptor signaling pathway
    		Toll-like receptor signaling pathway0.94
    		Regulation of toll-like receptor signaling pathway0.93
    		Toll-like receptor signaling pathway0.94
    		Hepatitis B0.31
    2NOD-like Receptor Signaling Pathways
    		Toll-Like receptor Signaling Pathways0.58
    		Inflammasome Activation Pathways0.51
    		NOD-like Receptor Signaling Pathways0.58
    		Immune response Role of TLRs 3 and 4 in cell antiviral response TICAM1 specific signaling pathways0.33
    3Cytosolic sensors of pathogen-associated DNA
    		RIP-mediated NFkB activation via ZBP10.81
    		Cytosolic sensors of pathogen-associated DNA0.38
    		ZBP1(DAI) mediated induction of type I IFNs0.81
    4Toll Like Receptor 7/8 (TLR7/8) Cascade
    		MyD88-independent cascade0.69
    		TRIF-mediated programmed cell death0.00
    		Toll Like Receptor 3 (TLR3) Cascade0.69
    5NF-KappaB Family Pathway
    		NF-KappaB (p50-p65) Pathway0.72
    		NF-KappaB Family Pathway0.72

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected R&D Systems Pathways for TLR3 (see all 6)
        NOD-like Receptor Signaling Pathways
    Inflammasome Activation Pathways
    IL-21 Signaling and its Primary Biological Effects in Different Immune Cell Types
    Th1 Differentiation
    Toll-Like receptor Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TLR3 (see all 9)
        NF-KappaB (p50-p65) Pathway
    Toll-Like Receptors Pathway
    TRAF Pathway
    TREM1 Pathway
    Colorectal Cancer Metastasis

    1 Cell Signaling Technology (CST) Pathway for TLR3
        NF-kappaB Signaling

    1 Tocris Bioscience Pathway for TLR3
        Toll-like Receptor Pathway

    1 GeneGo (Thomson Reuters) Pathway for TLR3
        Immune response TLR3 and TLR4 induce TICAM1-specific signaling pathway

    2 BioSystems Pathways for TLR3
        Toll-like receptor signaling pathway
    Regulation of toll-like receptor signaling pathway

    1 Sino Biological Pathway for TLR3
        NF-kB (NFkB) Pathway

    Selected Reactome Pathways for TLR3 (see all 8)
        TRIF-mediated programmed cell death
    IKK complex recruitment mediated by RIP1
    Toll Like Receptor 3 (TLR3) Cascade
    MyD88-independent cascade
    Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon


    5 Kegg Pathways  (Kegg details for TLR3):
        Toll-like receptor signaling pathway
    Hepatitis C
    Hepatitis B
    Influenza A
    Herpes simplex infection


    TLR3 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TLR3 (see all 8): 
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              Inflammatory Response & Autoimmunity in human mouse rat
              Inflammatory Response & Autoimmunity 384HT in human mouse rat
              Innate & Adaptive Immune Responses in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TLR3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TLR3 (O154551, 2, 3 ENSP000002967954) via UniProtKB, MINT, STRING, and/or I2D (see all 75)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PIK3R1P279861, 2, 3, ENSP000002743354EBI-6289595,EBI-79464 MINT-2840093 MINT-2840114 I2D: score=2 STRING: ENSP00000274335
    ENSG00000184494Q995193I2D: score=1 
    ENSG00000223957Q995193I2D: score=1 
    ENSG00000227129Q995193I2D: score=1 
    ENSG00000227315Q995193I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 52):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001934positive regulation of protein phosphorylation ----
    GO:0002224toll-like receptor signaling pathway TAS--
    GO:0002282microglial cell activation involved in immune response IEA--
    GO:0002756MyD88-independent toll-like receptor signaling pathway TAS--
    GO:0006952defense response ----

    TLR3 for ontologies           About GeneDecksing



    Drugs & Compounds
    for TLR3 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for TLR3
      Browse compounds at ApexBio 

    Compounds for TLR3 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    Pam2CSK4TLR2/6 agonist; induces TNF-alpha production[868247-72-7]
    ResiquimodToll-like receptor 7 (TLR7) agonist[144875-48-9]
    Pam3CSK4TLR1/2 agonist; induces cytokine production[112208-00-1]
    Poly(I:C)TLR3 agonist[42424-50-0]
    ImiquimodToll-like receptor 7 (TLR7) agonist[99011-02-6]

    1 IUPHAR Ligand for TLR3 (TLR3)    About this table
    LigandTypeActionAffinityPubmed IDs
    polyIC
    		AgonistAgonist11607032

    Selected Novoseek inferred chemical compound relationships for TLR3 gene (see all 22)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    poly(i-c) 92.4 66 16384532 (3), 15845391 (3), 16142732 (3), 14688319 (2) (see all 38)
    polyinosinic-polycytidylic acid 92.1 72 17962643 (4), 19452017 (4), 19154402 (2), 18949355 (2) (see all 36)
    flagellin 77 14 16365459 (1), 19294011 (1), 19955831 (1), 19740321 (1) (see all 14)
    inosine monophosphate 74.2 13 17182588 (3), 17573354 (1), 18715647 (1), 15196204 (1) (see all 11)
    peptidoglycan 68.8 16 16365459 (1), 17114468 (1), 16670332 (1), 14996826 (1) (see all 12)
    rantes 67.9 14 19121387 (3), 19452017 (2), 16436653 (1), 14517278 (1) (see all 9)
    lipoteichoic acid 58.1 4 17114468 (1), 15652398 (1), 16052591 (1), 16175622 (1)
    tab-2 52.8 3 14982987 (2), 12609980 (1)
    2',5'-oligoadenylate 52.8 2 17669408 (1)
    imiquimod 51.6 2 19578865 (1), 19643938 (1)

    1 PharmGKB related drug/compound annotation for TLR3 gene    About this table
    Drug/compound PharmGKB Annotation
    Measles vaccinesCA  



    TLR3 for compounds           About GeneDecksing



    Transcripts
    for TLR3 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for TLR3 gene: 
    NM_003265.2  

    Unigene Cluster for TLR3:

    Toll-like receptor 3
    Hs.657724  [show with all ESTs]
    Unigene Representative Sequence: BC068487
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000296795(uc003iyq.3) ENST00000513189 ENST00000512264(uc011ckz.2 uc003iyr.3)
    ENST00000504367 ENST00000508051
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Search for qRT-PCR Assays for microRNAs that regulate TLR3
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    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat TLR3
    Clone
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    OriGene ORF clones in mouse, rat for TLR3
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: TLR3 (NM_003265)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TLR3
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TLR3
    Primer
    Products:            		OriGene qPCR primer pairs and template standards for TLR3
    OriGene qSTAR qPCR primer pairs in human, mouse for TLR3
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat TLR3
      QuantiTect SYBR Green Assays in human, mouse, rat TLR3
      QuantiFast Probe-based Assays in human, mouse, rat TLR3

    Additional mRNA sequence: 

    AB445631.1 AK302143.1 AK314208.1 BC017954.1 BC043204.2 BC059372.1 BC068487.1 BC094737.1 
    BC096333.1 BC096334.3 BC096335.1 DQ445682.1 DQ470075.1 DQ470076.1 DQ470077.1 DQ470078.1 
    DQ470079.1 U88879.1 

    4 DOTS entries:

    DT.109361  DT.100664575  DT.101977909  DT.99984982 

    Selected AceView cDNA sequences (see all 50):

    BQ007482 CF529473 AU135937 NM_003265 BC068487 CF528559 BX104394 BI489939 
    CD109430 BF594247 BC059372 CB960574 BU624267 AL048899 CF994731 BX489678 
    BU929797 BU853465 CB989983 BF971051 BX489646 U88879 BG573455 BX495055 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for TLR3    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6
    SP1:                    -     -                           
    SP2:                          -                           
    SP3:                                                      


    ECgene alternative splicing isoforms for TLR3

    Expression
    for TLR3 gene

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    TLR3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CACTCTGTTT
    TLR3 Expression
    About this image


    TLR3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Blood (Cardiovascular System)
             Conventional Dendritic Cells I Spleen
     
     Spleen (Hematopoietic System)
             Conventional Dendritic Cells I Spleen
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Muscle Progenitor Cells Mandibular Arch Muscles
     
     Epithelial Cells
             Outer Root Sheath Cells Outer Root Sheath
     
     Hair (Integumentary System)
             Outer Root Sheath Cells Outer Root Sheath
    TLR3 Protein expression data from MOPED1, PaxDb2 and MaxQB3:     About this image

    TLR3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.657724

    UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455
    Tissue specificity: Expressed at high level in placenta and pancreas. Also detected in CD11c+ immature dendritic
    cells. Only expressed in dendritic cells and not in other leukocytes, including monocyte precursors. TLR3 is the
    TLR that is expressed most strongly in the brain, especially in astrocytes, glia, and neurons

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TLR3 (see all 8): 
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              Inflammatory Response & Autoimmunity in human mouse rat
              Inflammatory Response & Autoimmunity 384HT in human mouse rat
              Innate & Adaptive Immune Responses in human mouse rat

    Primer
    Products:    		OriGene qPCR primer pairs and template standards for TLR3
    OriGene qSTAR qPCR primer pairs in human, mouse for TLR3
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat TLR3
    QuantiTect SYBR Green Assays in human, mouse, rat TLR3
    QuantiFast Probe-based Assays in human, mouse, rat TLR3
    In Situ
    Assay Products:     
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TLR3

    Orthologs
    for TLR3 gene

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for TLR3 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    mouse
    (Mus musculus)    		 Mammalia Tlr31 , 5 toll-like receptor 31, 5 81.31(n)1
    79.93(a)1    		   8 (25.31 cM)5
    1429801  NM_126166.41  NP_569054.21 
     453956655 
    chicken
    (Gallus gallus)    		 Aves TLR31 toll-like receptor 3 66.82(n)
    61.8(a)    		   422720  NM_001011691.3  NP_001011691.3 
    lizard
    (Anolis carolinensis)    		 Reptilia TLR36
    		 toll-like receptor 3
    		 57(a)
    		 1 ↔ 1
    		 5(112305568-112319535)
    tropical clawed frog
    (Xenopus tropicalis)    		 Amphibia tlr31 toll-like receptor 3 59.31(n)
    55.86(a)    		   100486223  XM_002934402.2  XP_002934448.2 
    zebrafish
    (Danio rerio)    		 Actinopterygii tlr31 toll-like receptor 3 52.99(n)
    49.2(a)    		   403126  NM_001013269.3  NP_001013287.2 
    fruit fly
    (Drosophila melanogaster)    		 Insecta CG95623
    Tollo1    		 Tollo1 26(a)
    (best of 2)3
    42.12(n)1
    30.79(a)1    		   444971  NM_080018.21  NP_524757.11 


    ENSEMBL Gene Tree for TLR3 (if available)
    TreeFam Gene Tree for TLR3 (if available)

    Paralogs
    for TLR3 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TLR3 gene
    ENSG000001733662  CD1802  TLR72  TLR12  TLR92  TLR52  TLR102  TLR42  
    TLR82  TLR62  TLR22  
    1 SIMAP similar gene for TLR3 using alignment to 4 protein entries:     TLR3_HUMAN (see all proteins):
    TLR2

    TLR3 for paralogs           About GeneDecksing



    Genomic Variants
    for TLR3 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    TLR3_HUMAN, O15455: The Phe-412 allele (dbSNP:rs3775291) occurs with a frequency of 30% in populations with European and
    Asian ancestry, and confers some natural resistance to HIV-1 infection


    Selected SNPs for TLR3 (see all 466)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 4 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    VAR_0548874
    		Herpes simplex encephalitis 2 (HSE2)4--see VAR_0548872 P S mis40--------
    rs1214344311,2
    		C,Fother1186763303(+) GTGGTC/TCCATT 2 P S mis11Minor allele frequency- T:0.00NA 4550
    rs360276241,2
    		C--182754573(+) AAAAA-/A/AA  
                AAAAA     		1 -- int12NA CSA 4
    rs1153135991,2
    		C,F--186747149(+) GGACTC/GAAGTG 1 -- us2k11Minor allele frequency- G:0.05WA 118
    rs1395076741,2
    		--186747253(+) ACCACA/GTTGCC 1 -- us2k10--------
    rs1455860231,2
    		--186747290(+) AAGCAA/GTCTCC 1 -- us2k10--------
    rs752174671,2
    		C,F--186747300(+) CTAAAG/ATGTTG 1 -- us2k12Minor allele frequency- A:0.09CSA WA 120
    rs1829287491,2
    		--186747430(+) AATGTA/GCAGTA 1 -- us2k10--------
    rs1477253781,2
    		--186747470(+) AACTAA/GCAAGA 1 -- us2k10--------
    rs1870450181,2
    		--186747588(+) AAGTCA/GTGGGA 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for TLR3 (186990306 - 187009223 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for TLR3:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2677545CNV Deletion23128226
    dgv683n27CNV Gain19166990
    nsv470097CNV Gain18288195
    dgv5852n71CNV Gain21882294
    nsv881424CNV Gain21882294
    dgv5851n71CNV Gain21882294

    Human Gene Mutation Database (HGMD): TLR3
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing TLR3
    DNA2.0 Custom Variant and Variant Library Synthesis for TLR3

    Disorders / Diseases
    for TLR3 gene

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 603029   
    OMIM disorders: 613002  609423  
    UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455
  • Herpes simplex encephalitis 2 (HSE2) [MIM:613002]: A rare complication of human herpesvirus 1 (HHV-1)
    infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic
    necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache,
    seizures, stupor, and often coma, frequently with a fatal outcome. Note=Disease susceptibility is associated with
    variations affecting the gene represented in this entry. TLR3 mutations predispose otherwise healthy individuals
    to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced
    immune defense against viral infection in the central nervous system

    • Selected diseases for TLR3 (see all 107):    
    About MalaCards
    hiv1 infection    herpes simplex encephalitis 2    encephalitis    herpes simplex encephalitis
    measles    septic arthritis    west nile virus    herpes simplex encephalitis 1
    herpes simplex    allergic conjunctivitis    subacute sclerosing panencephalitis    pouchitis
    molluscum contagiosum    hyper ige syndrome    corneal disease    stevens-johnson syndrome
    tick-borne encephalitis    protein c deficiency    pandas    bronchiolitis

    5 diseases from the University of Copenhagen DISEASES database for TLR3:
    Encephalitis     Melanoma     Influenza     Herpes simplex
    Asthma

    TLR3 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for TLR3 gene (see all 29)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    virus infection 73.1 57 16877304 (2), 14575692 (2), 19452017 (2), 12672806 (2) (see all 36)
    inflammation 48.6 13 19752565 (2), 20387535 (2), 18403353 (1), 20483774 (1) (see all 9)
    hepatitis c chronic 38.3 1 19475618 (1)
    necrosis 32.7 9 14729660 (1), 15579900 (1), 16510559 (1), 18765427 (1) (see all 9)
    melanoma 32.1 27 17671143 (4), 19001446 (3), 19470740 (2), 17142768 (1) (see all 14)
    hepatitis c 30.8 3 19625408 (2), 18021446 (1)
    influenza 30.4 10 15579900 (3), 19231996 (3), 16399790 (2), 16517210 (1) (see all 5)
    bacterial infections 27.2 1 18083507 (1)
    herpes simplex 23.9 3 19025601 (1), 16847112 (1)
    pouchitis 20.9 3 16770571 (2)

    Genetic Association Database (GAD): TLR3
    Human Genome Epidemiology (HuGE) Navigator: TLR3 (55 documents)

    Export disorders for TLR3 gene to outside databases

    Publications
    for TLR3 gene

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

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    PubMed articles for TLR3 gene, integrated from 10 sources (see all 684):
    (articles sorted by number of sources associating them with TLR3)    		    Utopia: connect your pdf to the dynamic
    world of online information

    1. Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. (PubMed id 18753640)1, 2, 4, 9 Yang Z.... Zhang K. (N. Engl. J. Med. 2008)
    2. A family of human receptors structurally related to Drosophila Toll. (PubMed id 9435236)1, 2, 3 Rock F.L.... Bazan J.F. (Proc. Natl. Acad. Sci. U.S.A. 1998)
    3. TLR3 gene polymorphisms and liver disease manifestations in chronic hepatitis C. (PubMed id 19475618)1, 4, 9 Askar E....Mihm S. (J. Med. Virol. 2009)
    4. Investigation of the [-/A]8 and C1236T genetic variations within the human Toll-like receptor 3 gene for association with multiple sclerosis. (PubMed id 20483009)1, 4, 9 Szvetko A.L....Griffiths L.R. (Neurol. Res. 2010)
    5. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. (PubMed id 15961631)1, 2, 9 Choe J.... Wilson I.A. (Science 2005)
    6. Single-nucleotide polymorphisms in genes encoding toll-like receptor -2, -3, -4, and -9 in case-control study with breast cancer. (PubMed id 19810822)1, 4, 9 Etokebe G.E....DembiA8 Z. (Genet Test Mol Biomarkers 2009)
    7. Toll-like receptor polymorphisms and age-related macular degeneration. (PubMed id 18385087)1, 4, 9 Edwards A.O....Tosakulwong N. (amp 2008)
    8. Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals. (PubMed id 19855253)1, 4, 9 Pine S.O....Bochud P.Y. (AIDS 2009)
    9. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. (PubMed id 18946062)1, 4, 9 Bochud P.Y....Boeckh M. (N. Engl. J. Med. 2008)
    10. Innate immunity of the ocular surface and ocular surface inflammatory disorders. (PubMed id 18813073)1, 4, 9 Ueta M. (Cornea 2008)

    External Searches for TLR3 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section

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     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing TLR3 gene

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section

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    Entrez Gene: 7098 HGNC: 11849 AceView: TLR3 Ensembl:ENSG00000164342 euGenes: HUgn7098
    ECgene: TLR3 Kegg: 7098 H-InvDB: TLR3

    Other Databases showing TLR3 gene

    (According to HUGE)
    About This Section

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    Specialized Databases showing TLR3 gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for TLR3 Pharmacogenomics, SNPs, Pathways
    TLR3basehttp://bioinf.uta.fi/TLR3base/

    Intellectual Property
    for TLR3 gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

    TryGeneCards Plus    		Patent Information for TLR3 gene:
    Search GeneIP for patents involving TLR3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    Products
    for TLR3 gene

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